Dr. Rajashekhar Kanchanapally
Development of novel delivery-vehicle for breast cancer therapy
Cancer continues to be a leading cause of death in the United States. Cancer accounts for 15% of all death among women. Breast cancer is the most common type of cancer in American women. Surgery, radiation, and systemic therapy are some of the most popular methods for the treatment of breast cancer. Surgery and radiation therapy are option only when the cancer is detected in early stages and the disease is not metastasized, that means not spread to other organs of the body. Systemic therapy is the only option when the cancer is metastasized. However, systemic therapy is not targeted and therefore affects many of the normal cells, along with the cancer cells. The resulting side effects severely limits the amount of the drug that can be given to a patient. Paclitaxel is a very efficient drug that has been clinically used for a long time. However, Paclitaxel is insoluble in water-based solutions, and it has to be given to patients by formulating with other chemicals (excipients). These excipients are highly toxic and cause severe side effects. Recently, several nano-based drug delivery agents have been successfully used to treat multiple types of cancers. We hypothesize that loading Paclitaxel in natural nanoparticles, exosomes, will greatly reduce the side effects caused by traditional drug-delivery method. Moreover, modifying the exosomes with a cell penetrating agent will further enhance the efficiency of the delivery vehicle. We will test our hypothesis: first, by loading the Paclitaxel in cell-penetrating exosomes, followed by understanding its drug release kinetics; second, we will assess the cellular uptake, efficiency to induce apoptosis in cancer cells and toxicity towards normal cells of the proposed nanodelivery system; third, we will comprehensively evaluate the nano-delivery system’s efficiency in its anticancer activity and then correlate it with IC50 of liposomal and free forms of Paclitaxel. The data generated from the studies may pave the way for the potential use of proposed drug delivery system in clinics.